Objective To investigate the clinical characteristics and influencing factors of thyroid function abnormality (TFA) in patients with malignant tumors receiving programmed death-1 (PD-1) inhibitor therapy, and its correlation with PD-1 inhibitors. Methods A retrospective analysis was conducted on the clinical data and biochemical indicators of 669 patients with malignant tumors who received PD-1 inhibitor therapy. Of these, 561 patients maintained normal thyroid function (normal group), while 108 developed TFA (TFA group). Baseline characteristics, PD-1 inhibitor type, tumor type, and other indice were compared between the two groups. Univariate and multivariate logistic regression analyses were performed to identify related factors for TFA development. Additionally, the relationship between PD-1 inhibitors and TFA types was further analyzed within the TFA group. Results The rates of patients treated with pembrolizumab and with respiratory tumors were significantly higher in TFA group than those in the normal group (P＜0.01). Multivariate logistic regression analysis revealed that treatment with pembrolizumab and with respiratory tumor increased 5.350 and 1.514 times than tislelizumab and digestive tumor for risk of TFA development, respectively (P＜0.01). Within the TFA group, hypothyroidism was the predominant type (75, 69.4%); treatment with pembrolizumab increased 2.999 times than tislelizumab for development risk of hyperthyroidism (P＝0.042). Conclusions Among patients with malignant tumors treated with PD-1 inhibitors, pembrolizumab is more frequently associated with TFA, and patients with respiratory tumors were at a higher risk of developing TFA. Clinicians should closely monitor thyroid function in patients with respiratory tumors treated with pembrolizumab.

Abstract Prenatal stress is a common, systemic, nonspecific stress response that occurs during pregnancy. The gut microbiota, which is known as the “second genome” of the human body, interacts with all major systems of the body. Changes in the gut microbiota can impact the development and health of infants and young children. Advances in research technology have allowed us to uncover the relationship between prenatal stress and imbalances in offspring intestinal microbiota, as well as the development of multiple systemic diseases. However, the exact mechanisms through which prenatal stress disrupts the gut microbiota of offspring remain incompletely understood. This review summarizes the existing research on diseases caused by prenatal stress disrupting the offspring intestinal flora, and seeks future research directions to expand the understanding of the pathogenesis of infant diseases.

Objective:To explore the risk factors of short-term prognosis of severe Budd-Chiari syndrome (BCS) patients,established and verified the nomogram prediction model for these BCS patients and evaluated its clinical application value.Methods:This study is a retrospective cohort study. The clinical data of 171 patients with severe BCS diagnosed were retrospectively analyzed in the Department of Hepatopancreatobiliary Surgery First Affiliated Hospital of Zhengzhou University from January 2018 to December 2023. There were 105 males and 66 females, aged (52.1±12.8) years (range: 18 to 79 years). The patients were divided into two groups based on whether they died within 28 days: the death group ( n=38) and the survival group ( n=133). The risk factors for short-term death of patients were analyzed,and independent risk factors were screened by univariate and multivariate analysis. Furthermore,these factors were used to establish the nomogram prediction model. The area under the curve(AUC),the Bootstrap Resampling,the Hosmer-Lemeshow test and the Decision Curve Analysis(DCA) were used to verify the model′s differentiation,internal verification,calibration degree and clinical effectiveness,respectively. Results:Univariate and multivariate Logistics regression analysis showed that the history of hepatic encephalopathy,white blood cell,glomerular filtration rate and prothrombin time were independent risk factors ( P<0.05). The above factors were used to successfully establish the prediction model with 0.908 of AUC and 0.895 of the internal verification of AUC,indicating that the predictive model was valuable. The 0.663 P-values in the Hosmer-Lemeshow test indicated the high calibration degree of the model. The clinical effectiveness of the model was proved by the 18% clinical benefit population using the DCA curve with the 17% probability threshold. Conclusions:The independent risk factors are the history of hepatic encephalopathy,white blood cell,glomerular filtration rate and prothrombin time. An adequate basis was acquired by establishing a nomogram prediction model of the short-term prognosis of severe BCS,which was helpful for early clinical screening and identification of high-risk patients with severe BCS who could die in the short term and timely providing timely intervention measures for improving the prognosis.

Objective:To explore the clinical features and genetic basis for a child with Intellectual developmental disorder (IDD) and epilepsy.Methods:A child who was admitted to the Children′s Medical Center of the Affiliated Hospital of Guangdong Medical University in February 2021 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.Results:The patient, a 3-month-and-27-day female infant, had developed the symptoms in the neonatal period, which included severe developmental delay, respiratory difficulties and pauses, increased muscle tone of four limbs, feeding difficulty, and seizures. Cerebral MRI revealed bilateral cerebellar hypoplasia, and video EEG showed slightly increased sharp waves emanating predominantly from the right parietal, occipital, and posterior temporal regions. WES revealed that she has harbored a missense c. 3196G>A (p.Glu1066Lys) variant of the CLTC gene, which was confirmed to be de novo by Sanger sequencing. Based on the guideline from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PS2+ PM2_Supporting+ PP3). Conclusion:The c. 3196G>A (p.Glu1066Lys) missense variant of the CLTC gene probably underlay the pathogenesis in this child. Above finding has facilitated her diagnosis and treatment.

Objective:To explore the risk factors of short-term prognosis of severe Budd-Chiari syndrome (BCS) patients,established and verified the nomogram prediction model for these BCS patients and evaluated its clinical application value.Methods:This study is a retrospective cohort study. The clinical data of 171 patients with severe BCS diagnosed were retrospectively analyzed in the Department of Hepatopancreatobiliary Surgery First Affiliated Hospital of Zhengzhou University from January 2018 to December 2023. There were 105 males and 66 females, aged (52.1±12.8) years (range: 18 to 79 years). The patients were divided into two groups based on whether they died within 28 days: the death group ( n=38) and the survival group ( n=133). The risk factors for short-term death of patients were analyzed,and independent risk factors were screened by univariate and multivariate analysis. Furthermore,these factors were used to establish the nomogram prediction model. The area under the curve(AUC),the Bootstrap Resampling,the Hosmer-Lemeshow test and the Decision Curve Analysis(DCA) were used to verify the model′s differentiation,internal verification,calibration degree and clinical effectiveness,respectively. Results:Univariate and multivariate Logistics regression analysis showed that the history of hepatic encephalopathy,white blood cell,glomerular filtration rate and prothrombin time were independent risk factors ( P<0.05). The above factors were used to successfully establish the prediction model with 0.908 of AUC and 0.895 of the internal verification of AUC,indicating that the predictive model was valuable. The 0.663 P-values in the Hosmer-Lemeshow test indicated the high calibration degree of the model. The clinical effectiveness of the model was proved by the 18% clinical benefit population using the DCA curve with the 17% probability threshold. Conclusions:The independent risk factors are the history of hepatic encephalopathy,white blood cell,glomerular filtration rate and prothrombin time. An adequate basis was acquired by establishing a nomogram prediction model of the short-term prognosis of severe BCS,which was helpful for early clinical screening and identification of high-risk patients with severe BCS who could die in the short term and timely providing timely intervention measures for improving the prognosis.

Objective To investigate the correlation of serum oxytocin(PRL)and interleukin-38(IL-38)with type 2 diabetes mellitus(T2DM)combined with non-alcoholic fatty liver disease(NAFLD).Methods A total of 172 patients with T2DM admitted to the Department of Gastroenterology in the hospital from January 2021 to January 2023 were selected as the T2DM group and were divided into the NAFLD group(88 cases)and the non-NAFLD group(84 cases)according to whether or not they were comorbid with NAFLD,and 67 physically examined healthy people during the same period were also selected as the control group.Serum PRL and IL-38 levels were measured by enzyme-linked immunosorbent assay.Logistic regression was used to ana-lyze the factors affecting T2DM combined with NAFLD,and receiver operating characteristic(ROC)curve was used to analyze the predictive value of serum PRL and IL-38 for T2DM combined with NAFLD.Results Com-pared with the control group,serum PRL levels decreased and IL-38 levels increased in the T2DM group(P＜0.05).The NAFLD comorbidity rate was 51.16％(88/172)in 172 patients with T2DM.Compared with the non-NAFLD group,serum PRL levels decreased and IL-38 levels increased in the NAFLD group(P＜0.05).Increased body mass index,prolonged duration of T2DM,and elevated ghrelin aminotransferase,ghrelin amin-otransferase,total cholesterol,triacylglycerol,LDL cholesterol,and IL-38 were the independent risk factors for T2DM combined with NAFLD(P＜0.05),and elevated HDL cholesterol and PRL were the independent pro-tective factors(P＜0.05).The area under the curve for the combined prediction of serum PRL and IL-38 for T2DM combined with NAFLD was 0.897,which was greater than 0.779 and 0.782 of serum PRL and IL-38 alone(P＜0.05).Conclusion Reduced serum PRL levels and increased IL-38 levels in T2DM patients are in-dependent influencing factors for T2DM combined with NAFLD,and the combination of serum PRL and IL-38 has a high predictive value for T2DM combined with NAFLD.

Objective To retrospectively analyze of factors influencing early preterm birth(EPB)and late preterm birth(LPB)in pregnancy women with placenta previa complicated by placenta accreta spectrum disorders(PAS),and assess maternal and infant outcomes.Methods We included 590 cases of pregnancy women with placenta previa complicated by PAS who underwent cesarean sections at five hospitals in Wuhan and Xianning cities between January 2018 and June 2021.These patients were divided into three groups based on delivery gesta-tional age:EPB,LPB,and term birth(TB).A multiple logistic regression model was employed to analyze the risk factors associated with EPB and LPB.Additionally,differences in early maternal and infant outcomes among these groups were examined.Results Among 590 pregnancy women with placenta previa complicated by PAS,the proportions of EPB and LPB were 9.7%and 54.4%.The use of uterine contraction inhibitors prior to cesarean section,vaginal bleeding,and previous cesarean sections history were identified as risk factors for both EPB and LPB.The proportion of severe postpartum hemorrhage was comparable between the EPB group and the LPB group;however,the incidence of neonatal asphyxia,low birth weight infants,and the rate of newborns transferred to the Neonatal Intensive Care Unit(NICU)within 24 hours after cesarean delivery were significantly higher in the EPB group compared to the LPB group.Conclusions Placenta previa complicated by PAS predominantly leads to LPB.The history of prior cesarean sections,uterine contractions,and vaginal bleeding prior to cesarean section,are sig-nificantly associated with both EPB and LPB.During the perinatal period,efforts should be made to extend gesta-tional weeks under close monitoring to minimize the incidence of premature births and thereby improve early mater-nal and infant outcomes.

Objective:To study the clinical value of the Naples prognostic score (NPS) in predicting the prognosis of patients with intrahepatic cholangiocarcinoma (ICC) after radical resection and establish a nomogram prediction model.Methods:Clinical data of 77 patients with ICC undergoing radical hepatectomy for the first time in the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2022 were retrospectively collected, including 46 males and 31 females, aged (58.9±11.0) years old. The area under the receiver operating characteristic curve for NPS to predict the death after radical hepatectomy in ICC patients was 0.673, and the optimal cut-off value for NPS based on the Youden's index was 2.5. According to the optimal cut-off value of NPS, patients were divided into two groups: the low NPS group (patients with NPS≤2.5, n=37) and high NPS group (patients with NPS>2.5, n=40). The clinicopathological data including resection extent, blood transfusion, tumor differentiation, lymphovascular invasion, lymph node metastasis and postoperative complications were compared between the groups. Follow-ups were conducted via outpatient or telephone reviews. Kaplan-Meier method was used for survival analysis, and log-rank test was used for survival comparison. Cox proportional hazards regression was used to analyze the risk factors affecting postoperative survival. A prediction nomogram was established and evaluated. Results:Compared to the low NPS group, the proportion of patients with tumor length ≥5 cm, lymphovascular invasion, lymph node metastasis, tumor carbohydrate antigen 19-9 ≥37 U/ml and the level of neutrophil to lymphocyte ratio were increased in the high NPS group, while the proportion of patients with serum albumin ≥40 g/L was decreased (all P<0.05). The cumulative survival rate of patients in the high NPS group was lower than that of the low NPS group ( P=0.001). Multivariate Cox analysis showed that ICC patients with lymphovascular invasion, lymph node metastasis, and NPS>2.5 had a higher risk of short survival after surgery (all P<0.05). The nomogram model based on NPS has a good predictive capacity. Conclusion:High preoperative NPS score indicates poor postoperative prognosis, and NPS score is an independent risk factor affecting the prognosis of ICC patients.

Background: Diabetes-induced cardiac fibrosis is one of the main mechanisms of diabetic cardiomyopathy. As a common histone methyltransferase, enhancer of zeste homolog 2 (EZH2) has been implicated in fibrosis progression in multiple organs. However, the mechanism of EZH2 in diabetic myocardial fibrosis has not been clarified. Methods: In the current study, rat and mouse diabetic model were established, the left ventricular function of rat and mouse were evaluated by echocardiography and the fibrosis of rat ventricle was evaluated by Masson staining. Primary rat ventricular fibroblasts were cultured and stimulated with high glucose (HG) in vitro. The expression of histone H3 lysine 27 (H3K27) trimethylation, EZH2, and myocardial fibrosis proteins were assayed. Results: In STZ-induced diabetic ventricular tissues and HG-induced primary ventricular fibroblasts in vitro, H3K27 trimethylation was increased and the phosphorylation of EZH2 was reduced. Inhibition of EZH2 with GSK126 suppressed the activation, differentiation, and migration of cardiac fibroblasts as well as the overexpression of the fibrotic proteins induced by HG. Mechanical study demonstrated that HG reduced phosphorylation of EZH2 on Thr311 by inactivating AMP-activated protein kinase (AMPK), which transcriptionally inhibited peroxisome proliferator-activated receptor γ (PPAR-γ) expression to promote the fibroblasts activation and differentiation. Conclusion Our data revealed an AMPK/EZH2/PPAR-γ signal pathway is involved in HG-induced cardiac fibrosis.

The value of combined detection of neutrophil apolipoprotein (HNL), serum amyloid A (SAA), procalcitonin (PCT) and C-reactive protein (CRP) in the differential diagnosis of bacterial and viral infectious diseases. A retrospective study was conducted to collect the clinical data of infected patients and healthy people in the clinical department of Shaanxi Provincial People's Hospital from September to December in 2022. 100 patients with confirmed infection were divided into bacterial infection group (n=50) and virus infection group (n=50), and 50 healthy people were selected as control group (n=50). Fasting venous blood was collected at the initial stage of admission or on the day of physical examination. HNL was detected by double antibody sandwich method, SAA and CRP were detected by nephelometry, and PCT was detected by chemiluminescence method. The efficacy of infection markers in the differential diagnosis of bacterial infection and viral infection in infected patients was evaluated. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of HNL, SAA, PCT and CRP in bacterial and viral infectious diseases; Logistic regression was used to analyze the influence of each index on the diagnostic efficiency. The results showed that the levels of HNL (126.60±33.32) ng/ml, PCT (28.02±11.37) ng/ml and CRP (36.13±14.37) mg/L in bacterial infection group were significantly higher than those of HNL (47.72±15.94) ng/ml, PCT (1.27±0.40) ng/ml, CRP (18.77±10.66) mg/L in virus group and HNL (38.21±12.53) ng/ml, PCT (0.38±0.12) ng/ml and CRP (4.13±1.07) mg/L in control group. The level of HNL increased most significantly (F=89.228, P<0.05). The area under ROC curve (AUC) from large to small was HNL+SAA+PCT+CRP (0.976), HNL (0.907), PCT (0.885), CRP (0.856), SAA (0.790), SAA/CRP (0.733). The level of SAA/CRP in virus infection group (94.05±3.75) was significantly higher than that in bacteria group (17.70±3.69) and control group (3.89±1.50) (F=84.005, P<0.05). The area under ROC curve (AUC) from large to small was HNL+SAA+PCT+CRP (0.986), SAA/CRP (0.956), SAA (0.878), HNL (0.768), CRP (0.742), PCT (0.730). In conclusion, HNL has the best auxiliary diagnostic efficacy in bacterial infection, followed by PCT; SAA/CRP has the best auxiliary diagnostic efficacy in viral infection, followed by SAA; the combined detection of serum HNL, SAA, PCT and CRP may be helpful for the differential diagnosis of bacterial and viral infections.
Humans ; C-Reactive Protein ; Procalcitonin ; Serum Amyloid A Protein ; Retrospective Studies ; Virus Diseases/diagnosis* ; Bacteria ; Communicable Diseases ; Bacterial Infections/diagnosis*